The murine model MAIDS is used to ask fundamental questions about the mechanisms of retroviral pathogenesis. MAIDS induces a immunosuppression of both B and T lymphocyte responses, polyclonal B cell activation and hypergammaglobulinemia, lymphadenopathy, increased susceptibility to opportunistic infections and an increased incidence of non-Hodgkin's B cell lymphomas. The overall goals of this proposal are to examine: (1) CD40L mediated signaling o B cells leading to their activation, hypergammaglobulinemia and ultimately B cell tumors; (2) the specificity of cytotoxic T cells (CTL) responses of MAIDS-resistant mouse strains or to an immunodominant gag epitope; and (3) the potential contribution of open reading frame (ORF2) directed expression of this gag epitope. The experimental approach utilizes CD40 or CD40L knock out mice to examine the role of these molecules in the genesis of disease, and mutational analysis of ORF2 and CTL epitopes to examine immune resistance and susceptibility.